Infrequent and low expression of cancer-testis antigens located on the X chromosome in colorectal cancer: implications for immunotherapy in South African populations.
Cancer-testis (CT) antigens are a group of tumor antigens that are expressed in the testis and aberrantly in cancerous tissue but not in somatic tissues. The testis is an immune-privileged site because of the presence of a blood-testis barrier; as a result, CT antigens are considered to be essentially tumor specific and are attractive targets for immunotherapy. CT antigens are classified as the CT-X and the non-X CT antigens depending on the chromosomal location to which the genes are mapped. CT-X antigens are typically highly immunogenic and hence the first step towards tailored immunotherapy is to elucidate the expression profile of CT-X antigens in the respective tumors. In this study we investigated the expression profile of 16 CT-X antigen genes in 34 colorectal cancer (CRC) patients using reverse transcription-polymerase chain reaction. We observed that 12 of the 16 CT-X antigen genes studied did not show expression in any of the CRC samples analyzed. The other 4 CT-X antigen genes showed low frequency of expression and exhibited a highly variable expression profile when compared to other populations. Thus, our study forms the first report on the expression profile of CT-X antigen genes among CRC patients in the genetically diverse South African population. The results of our study suggest that genetic and ethnic variations in population might have a role in the expression of the CT-X antigen genes. Thus our results have significant implications for anti-CT antigen-based immunotherapy trials in this population.
Dakshinamurthy
Amirtha Ganesh
AG
Department of Biotechnology, University of the Western Cape, Cape Town, South Africa.
Ramesar
Rajkumar
R
Goldberg
Paul
P
Blackburn
Jonathan M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013019:South Africa; D013737:Testis / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins; C454199:DDX53 protein, human; D053487:DEAD-box RNA Helicases